Textbook of Personalized Medicine - Second Edition [2015]

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Current Therapies of HIV/AIDS

A variety of therapies have been developed for persons infected with HIV. Bone
marrow transplantation, lymphocyte transfusions, thymic transplantation, and ther-
apeutic apheresis to remove virus-bearing cells were tried without signifi cant suc-
cess against HIV infection and are no longer employed. Current therapeutic
strategies for intervening in HIV-1 disease include the following:

• Antiretroviral chemotherapeutic agents


• Treatment and prophylaxis of opportunistic infections


• Treatment of other complications including tumors

AIDS has been treated with chemotherapeutic agents that act at various key
points in the life cycle of HIV (Fig. 11.2 ). These include nucleoside reverse tran-
scriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors
(NNRTIs) and protease inhibitors (PIs). NRTIs remain a cornerstone of current anti-
retroviral regimens in combinations usually with a NNRTI, a PI, or an INI.
According to International AIDS Society’s guidelines for the use of antiretrovi-
ral therapy in adult HIV infection, therapy should be initiated before CD4 cell count
declines to <350/μL. In patients that have 350 CD4 cells/μL or more, the decision
to begin therapy should be individualized based on the presence of comorbidities,
risk factors for progression to AIDS and non-AIDS diseases, and patient readiness
for treatment. In addition to the prior recommendation that a high plasma viral load
(e.g. >100,000 copies/mL) and rapidly declining CD4 cell count (>100/μL per year)
should prompt treatment initiation, active HBV or HCV coinfection, cardiovascular
disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy.
The initial regimen must be individualized, particularly in the presence of comorbid
conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibi-
tor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or
abacavir/lamivudine). Treatment failure should be identifi ed and managed promptly,
with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA
level below assay detection limits.

Attachment

to receptor

and entry

Reverse

transcription

RNA to DNA

Integration of viral

DNA into

host DNA

Maturation of

infectious viral

particles

Budding and

release of virus

Reverse

transcriptase

inhibitors

Entry

inhibitors

Integrase

inhibitors

Protease

inhibitors

HIV-1 life cycle

Anti-HIV approaches

Fig. 11.2 Mode of action of some current anti-HIV drugs

Personalized Management of Viral Infections